Hendriks et al.

BMC Musculoskeletal Disorders 2014, 15:346

http://www.biomedcentral.com/1471-2474/15/346

RESEARCH ARTICLE Open Access

Type 2 diabetes seems not to be a risk factor for

the carpal tunnel syndrome: a case control study
Steven H Hendriks1*, Peter R van Dijk1, Klaas H Groenier1,2, Peter Houpt3, Henk JG Bilo1,4 and Nanne Kleefstra1,4,5

Abstract
Background: Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in
patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular
complications and degree of glycaemic control. Primary aim was to determine if type 2 diabetes can be identified
as a risk factor for carpal tunnel syndrome after adjusting for possible confounders. Furthermore, the influence of
duration of diabetes mellitus, microvascular complications and glycaemic control on the development of carpal
tunnel syndrome was investigated.
Methods: Retrospective, case–control study using data from electronic patient charts from the Isala (Zwolle, the
Netherlands). All patients diagnosed with carpal tunnel syndrome in the period from January 2011 to July 2012
were included and compared with a control group of herniated nucleus pulposus patients.
Results: A total of 997 patients with carpal tunnel syndrome and 594 controls were included. Prevalence of
type 2 diabetes was 11.5% in the carpal tunnel syndrome group versus 7.2% in the control group (Odds
Ratio 1.67 (95% confidence interval 1.16-2.41)). In multivariate analyses adjusting for gender, age and body
mass index, type 2 diabetes was not associated with carpal tunnel syndrome (OR 0.99 (95% CI 0.66-1.47)).
No differences in duration of diabetes mellitus, microvascular complications or glycaemic control between
groups were detected.
Conclusion: Although type 2 diabetes was more frequently diagnosed among patients with carpal tunnel
syndrome, it could not be identified as an independent risk factor.
Keywords: Carpal tunnel syndrome, Type 2 diabetes mellitus, Risk factor

Background
Carpal tunnel syndrome (CTS) is one of the most fre-
quent compression neuropathies of the upper limb [1].
Due to entrapment of the median nerve between the
flexor tendons of the hand in the carpal tunnel symp-
toms, like tingling and noctural burning pain, occur [1].
The combination of these clinical symptoms together
with positive signs by physical examination and nerve
conduction studies (NCS) is the most valid way of diag-
nosing CTS [1].
The prevalence of CTS in the general population is
approximately 2.1% for men and 3.0% for women [2].
Obesity, hypothyroidism, pregnancy, rheumatoid arthritis,
osteoarthritis and occupational factors like repetitive work
* Correspondence: s.hendriks@isala.nl
1
Diabetes Centre, Isala, Zwolle, the Netherlands
Full list of author information is available at the end of the article
are identified as the main risk factors for CTS [1]. In
addition, diabetes mellitus (DM) is also considered as a
risk factor [3-7]. Furthermore some researchers found a
higher incidence of CTS in patients with pre-diabetes [8],
nevertheless screening for DM in patients with CTS is not
recommended [9]. Literature suggests also a relationship
between HbA1c, duration of DM, microvascular compli-
cations and CTS [10-12]. However, many studies investi-
gated DM as a risk factor for musculoskeletal disorders of
the hand and shoulder in general and not for CTS in par-
ticular [11,13].
Aim of the present study was to determine if type 2
diabetes mellitus (T2DM) can be identified as a risk
factor for CTS. Furthermore, we investigated the influence
of diabetes duration, glycaemic control and presence of
microvascular complications on the development of CTS.

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Hendriks et al. BMC Musculoskeletal Disorders 2014, 15:346
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Methods
Study population and design
This study was conducted at the Isala, a general hospital
with a catchment area of 800.000 inhabitants in the
North East of the Netherlands. All patients with severe
symptoms of CTS or with symptoms which could not
be treated by a general practitioner with a conservative
approach (i.e. watchful waiting, a brace or corticoster-
oid injections) and who were referred to the outpatient
clinic of the Isala between January 2011 and July 2012
were identified. The diagnosis CTS was defined as the
presence of classical symptoms for CTS consisting of
nocturnal pain associated with tingling and numbness
in the distribution of median nerve in the hand. Patients
were only included when NCS were performed during the
diagnostic process of CTS, irrespective of the outcome of
the NCS. NCS were executed by a neurologist and con-
sisted of 1 motor and 2 sensory conduction tests. A com-
parison was made of the distal motor latencies from the
median nerve to the second lumbrical and from the ulnar
nerve to the second interosseous muscle with equal dis-
tances. Furthermore, a comparison was made of the sen-
sory conduction of the median nerve with the ulnar nerve
between wrist and digit 4 and of the sensory conduction
of the median with the radial nerve between wrist and
thumb. If two of three tests were abnormal, the diagnosis
of CTS was electrophysiologically confirmed. All nerve
conduction studies were performed with a Synergy system
of Viasys Healthcare from 2005 without controlling for
the hand temperature. Patients with an (ipsi and/or
contralateral) recidive of a previous CTS were excluded.
In order to compare the prevalence of T2DM among
patients with CTS with the general population, a control
group was formed consisting of operatively treated herni-
ated nucleus pulposus (HNP) patients. HNP patients were
chosen assuming that HNP patients would be derived
from about the same age category as the CTS group and
because it is a frequently diagnosed disease which makes
it possible to build a control group consisting of enough
patients. Finally only operated patients were chosen be-
cause DM status and BMI data are known for the majority
of operated patients in our hospital. Patients in the control
group were treated in the same period as the CTS group.
They were excluded when they received an operation
because of a relapse or had received the diagnosis CTS
in the past.
Data sources
Patients, both CTS cases and the HNP controls, were
identified using diagnosis-treatment-combination (DTC)
codes, which are used in the Netherlands for both hospital
registration and health insurance declaration purposes.
Each DTC code contains information about the specialty
of the treating physician, the patient’s diagnosis and the
Page 2 of 5
type of treatment provided. CTS patients were identified
using codes 0304.350, 0304.351 and 0330.0801 and HNP
patients using the codes 0308.2530, 0308.2550, 0308.2555.
The DTC codes for DM and diabetic retino-pathie were
used to identify patients with T2DM who are treated in
our clinic.
Demographic and clinical data of the CTS and HNP pa-
tients treated in the Isala was derived from the individual
electronic patient database of the Isala. Furthermore this
database was used to verify the CTS and HNP diagnoses.
The diabetes specific database of our Diabetes Centre was
used for identifying and further detailing of information
regarding patients with T2DM who are treated in primary
care. General practitioners in our region, receive bench
mark information from our Diabetes Centre and therefore
we gather data of all primary care treated patients with
T2DM on a yearly basis. This database is used in our
Diabetes Centre for study purposes. Permission to use the
CTS and HNP related data was given by de data manage-
ment centre of the Isala.
Variables
Age, gender, body mass index (BMI) and blood pressure
were documented for all patients. Date of CTS diagnosis,
CTS side, result of nerve conduction studies and type of
treatment were recorded in the database for CTS patients.
Duration of DM, types of medication, HbA1c, renal func-
tion and the occurrence of albuminuria, retinopathy and
neuropathy were documented for all T2DM patients.
Outcome
Primary outcome was the prevalence of T2DM in both
groups. Secondary outcomes were duration of DM, micro-
vascular complications (albuminuria, retinopathy and
neuro-pathie together) and glycaemic control in relation to
CTS development.
Statistical analysis
Statistical analysis was carried out in SPSS (version 20)
using logistic regression, adjusting for confounding vari-
ables. Multiple imputation (10 imputed datasets) was used
for missing BMI values. The sample size required for the
control group to detect a difference in T2DM prevalence
of 5%, assuming a CTS group size of 900 patients, a power
of 0.8, and an alpha of 0.05 was 459.
Ethical approval
This study is performed in accordance with the Declar-
ation of Helsinki. According to Dutch guidelines this
research does not fall under the scope of the Medical
Research Involving Human Subjects Act, and therefore
this study does not need a formal approval of an accre-
dited METC (The Medical Ethics Committee of the
Isala).
Hendriks et al. BMC Musculoskeletal Disorders 2014, 15:346
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Results
A total of 1482 patients with a DTC for CTS and 765
patients with a DTC for HNP were identified of which
485 CTS patients and 171 HNP controls did not meet the
inclusion criteria (Figure 1). Eventually, 997 persons with
CTS and 594 controls were included.
Primary outcome
The results of the univariate analyses are presented in
Table 1. The prevalence of T2DM was 11.5% in the CTS
group and 7.2% in the control group (Odds Ratio (OR)
1.67 (95% confidence interval (CI) 1.16-2.41)). The per-
centage of female patients was significantly higher in the
CTS group compared with the control group (OR 2.54
(95% BI 2.06-3.14), p <0.001). The mean age was 55.7
(±15.2) years in the CTS group and 49.3 (±13.0) years in
the control group (p <0.001). Furthermore, the mean BMI
was also higher in the CTS group (p <0.001).
Five hundred sixty-seven (56.9%) patients had a bilateral
CTS and 430 patients had an unilateral CTS of whom 252
(58.6%) right-sided. In 921 (92.4%) subjects diagnosis was
confirmed by NCS. Treatment consisted in 18.3% of con-
servative treatment, in 78.1% of operation and was not
well documented in 3.6% of the patients. Four hundred
twenty-one patients in the control group had a herniated
disc at the lumbar spine level and 173 patients had a her-
niated disc at the cervical level.
Table 2 displays the results of the multivariate analyses.
In model 1 (adjusting for gender) and in model 2 (adjust-
ing for both gender and BMI) T2DM was a significant
predictor for CTS. However, when age was added (model 3),
T2DM disappeared as a significant predictor (OR 0.99
(95% BI 0.66-1.47)). Gender, BMI and age remained
significant predictors for CTS in this final model. The
same results were obtained when only patients with
CTS confirmed by nerve conduction studies were in-
cluded (data not shown).
Figure 1 Flowchart inclusion.
Page 3 of 5
Secondary outcomes
Analyses of the subgroups with T2DM are also displayed
in Table 1. The CTS group contained 115 patients with
T2DM versus 43 patients with T2DM in the control
group. Patients in the CTS group were significantly older
and had a higher BMI. Duration of DM, presence of
microvascular complications and glycaemic control did
not differ between the two groups.
Discussion
In this study we investigated the relationship between
T2DM and CTS. Although T2DM was more frequently
diagnosed among patients with CTS, it could not be
identified as a risk factor after adjusting for BMI, gender
and age. However, BMI, gender and age remained having
a relationship with CTS. No associations were found be-
tween the duration of DM or microvascular complica-
tions and CTS. In addition, as demonstrated previously,
we were unable to find a relationship between glycaemic
control and CTS development [11].
This is the first study to investigate the relation between
CTS and T2DM in a secondary care setting. Strengths of
this study include the use of different data sources to over-
come limitations of the retrospective design (i.e. misclassi-
fication of CTS diagnosis and missing data). In addition,
the use of different data sources enabled us to make a cer-
tain diagnosis of CTS and T2DM.
Several limitations should be mentioned. First, cases
and controls were only enrolled in a secondary care set-
ting and thereby mostly severe cases were included.
Thus, less severe CTS patients treated with conservative
treatment by general practitioners did not participate in
the current study. Therefore the generalizability of our
results is limited to secondary care. In addition, external
validity is also limited due to the fact that the studied
population consisted of only ~1% of the DM and ~11%
of the CTS patients of the total amount of DM and CTS
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Table 1 Results of univariate analyses between the CTS group and the control group
Variables CTS group Control group p-value OR (95% CI)
(n =997) (n =594)
T2DM 115 (11.5) 43 (7.2) 0.006 1.67 (1.16-2.41)
Gender (female) 710 (71.2) 293 (49.3) <0.001 2.54 (2.06-3.14)
Age (years) 55.7 ± 15.2 49.3 ± 13.0 <0.001 1.03 (1.02-1.04)
BMI (kg/m2)a 28.3 ± 5.4 26.7 ± 4.6 <0.001 1.06 (1.04-1.09)
Systolic RR (mmHg) 138.8 ± 21.4 138.6 ± 20.6 0.870 1.00 (0.99-1.01)
Age DM patients (years) 65.6 ± 12.7 60.1 ± 13.7 0.021 1.03 (1.01-1.06)
Gender DM patients (female) 74 (64.3%) 21 (48.8%) 0.078 1.89 (0.93-3.84)
BMI DM patients (kg/m2) 31.2 ± 5.7 29.1 ± 5.1 <0.001 1.07 (1.04-1.10)
Median diabetes duration (months)b 103 (55–172) 80 (47–166) 0.389 1.00 (1.00-1.01)
c
HbA1c (% (mmol/mol)) 7.1 ± 3.2 (54 ± 11) 7.3 ± 3.2 (56 ± 12) 0.567 0.99 (0.95-1.03)
Microvascular complicationsd 46 (40.0%) 13 (30.2%) 0.402 0.68 (0.28-1.67)
Metformin 69 (60.0%) 26 (60.5%) 0.582 1.15 (0.70-1.89)
SU-derivate 34 (29.6%) 7 (16.3%) 0.09 2.19 (0.89-5.40)
Insulin 52 (45.2%) 18 (41.9%) 0.673 1.17 (0.57-2.37)
Values are depicted as number (%), mean ± SD or median with 25th and 75th percentile.
a
Imputation was used for 229 patients with a missing value for BMI in the CTS group and for 12 controls.
b
2 missing values in the CTS group and 16 in the control group.
c
6 missing values in the CTS group and 20 in the control group.
d
12 missing values in the CTS group and 19 the control group.

patients in our region. Moreover, although both the op- consultation. The choice to use surgery-treated HNP pa-
erated CTS and HNP patients had the same kind of pre- tients as a control population is also a topic for debate.
operative screening in which the presence of DM was Smaller studies have described a relationship between
assessed, we cannot exclude the possibility of more in- DM and HNP, so although inconclusive, the prevalence
tensive screening in one of the two groups which may of T2DM could be higher among these persons than in
have resulted in a different DM prevalence within and the general population [14]. Additionally, as overweight
between the two groups. Furthermore, differential mis- is identified as a risk factor for the occurrence of lumbar
classification bias could have occurred because conser- disc herniation, and overweight is also is a major risk
vatively treated CTS patient have had no preoperatively factor for T2DM, this could have resulted in a higher
prevalence of DM in the HNP population compared
Table 2 Multivariate analysis of T2DM as an risk factor with the general population [15,16]. Therefore, shared
for CTS adjusting for gender, age and BMI risk factors, such as BMI, should be taken into account
model (n =1591) B p-value OR (95% CI) when interpreting the results of our study. At last, it
Model 1 should be noticed that, due to the amount of missing
T2DM 0.571 0.003 1.77 (1.22-2.58) data any relevant relationships cannot be excluded based
Gender a
0.945 <0.001 2.57 (2.08-3.18) on the present study.
Similar to our results, a study among 156 CTS patients
Model 2
and 473 age and sex matched controls derived from a
T2DM 0.389 0.048 1.48 (1.00-2.17)
Dutch population register could not find a relation be-
Gendera 0.953 <0.001 2.59 (2.09-3.22) tween DM and CTS [17]. Furthermore, a study from
b
BMI 0.060 <0.001 1.06 (1.04-1.09) Greece found an identical prevalence of DM in a CTS
Model 3 population as compared to control subjects from the gen-
T2DM −0.014 0.946 0.99 (0.66-1.47) eral population [18]. On the other hand a significant rela-
tion was found in a larger cohort of 3391 CTS patients
Gendera 0.976 <0.001 2.65 (2.13-3.31)
and 13.564 matched controls (OR 1.51 (95% BI 1.24-1.84))
Age 0.034 <0.001 1.03 (1.03-1.04)
[4]. A systematic review indicated DM as a risk factor for
BMIb 0.064 <0.001 1.07 (1.04-1.09) CTS (OR 2.2 (95% BI 1.5-3.1)) [3]. However, not all stud-
B = coefficient of logistic regression.
a
ies included in this review controlled for age differences in
Male gender is reference category.
b
Imputation was used for 229 patients with a missing value for BMI in the CTS
multivariate models, which was found to be an important
group and for 12 controls. confounding variable in the present study.
Hendriks et al. BMC Musculoskeletal Disorders 2014, 15:346
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Taken together, it could be hypothesized that BMI and
age, both well known risk factors for T2DM, are import-
ant risk factors for CTS as well, and may explain the rela-
tionship found between T2DM and CTS in other studies.
Despite the limitations of the present study, i.e. choice of
control group, limited generalizability due to the second-
ary setting, magnitude of missing data and small sample
size, this is a hypothesis worth further testing.
Conclusion
Although type 2 diabetes was more frequently diagnosed
among patients with carpal tunnel syndrome, it could not
be identified as an independent risk factor. BMI and age,
which are well known risk factors for T2DM, are import-
ant risk factors for CTS as well and may confound the
previously found relationship between type 2 diabetes and
CTS.
Abbreviations
CTS: Carpal tunnel syndrome; DM: Diabetes mellitus; T2DM: Type 2 diabetes
mellitus; NCS: Nerve conduction studies; HNP: Herniated nucleus pulposus;
DTC: Diagnosis-treatment-combination; BMI: Body mass index; OR: Odds ratio;
CI: Confidence interval.
Competing interests
All authors declare that they have no competing interests.
Authors’ contributions
SHH (guarantor), PRD, KHG, PH, HJGB and NK designed the study; SHH and
PRD acquired the data used in this study; SHH, PRD and NK analysed the
data; SHH and KHG performed the statistical analyses; SHH and PRD drafted
the manuscript. SHH, PRD, KHG, PH, HJGB and NK participated in
interpretation of the data and in revision of the manuscript. All authors read
and approved the final manuscript. PRD, NK and HJGB supervised the study.
Acknowledgements
Steven H. Hendriks is the guarantor of this work and, as such, had full access
to all the data in the study and takes responsibility for the integrity of the
data and the accuracy of the data analysis.
Author details
1
Diabetes Centre, Isala, Zwolle, the Netherlands. 2Department of General
Practice, University of Groningen, Groningen, the Netherlands. 3Department
of Plastic Surgery, Isala, Zwolle, the Netherlands. 4Department of Internal
Medicine, University of Groningen, Groningen, the Netherlands. 5Langerhans,
Medical Research Group, Zwolle, the Netherlands.
Received: 25 February 2014 Accepted: 3 October 2014
Published: 14 October 2014
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doi:10.1186/1471-2474-15-346
Cite this article as: Hendriks et al.: Type 2 diabetes seems not to be a
risk factor for the carpal tunnel syndrome: a case control study. BMC
Musculoskeletal Disorders 2014 15:346.
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